tbuckley/cabot-search huggingface dataset:
Case 20-2022: A 25-Year-Old Man with Vision Changes
Authors: Zachariah DeFilipp, Karen Rodriguez, Judith A. Ferry
Journal: New England Journal of Medicine (2022)

A 25-year-old man with a history of leukemia and hematopoietic-cell transplantation was evaluated for vision changes. MRI revealed white-matter lesions; PET-CT showed FDG-avid lymphadenopathy. A diagnostic test was performed.
P1097: MEK-INHIBITORS IN TREATMENT OF LANGERHANS CELL HISTIOCYTOSIS
Authors: E. Burtsev, G. Bronin
Journal: HemaSphere (2022)

Background: There are increasing data of targeted therapy efficacy of different types of Langerhans cell histiocytosis (LCH) with inhibitors of BRAF-specific serin-threonine kinase (BRAF-inhibitors) in cases with BRAFV600e mutation published last years. At the same time there are lack of published data of MAPK/ERK pathway inhibitors (MEK-inhibitors) use in pediatric patients with BRAF-negative forms of LCH. Aims: Aim of the study is to evaluate efficacy and safety of MEK-inhibitor (cobimetinib) in eight pediatric BRAFV600e-negative refractory LCH patients. Methods: The study included 8 children with various forms of LCH. BRAFV600e mutation was not found in any case included in the trial. All patients received therapy according to the LCH IV protocol and were diagnosed with progression of LCH during or after termination of the treatment. Monotherapy with cobimetinib was used as a second line therapy in all cases. The response to the targeted therapy was assessed in accordance with the international scale Response Evaluation Criteria in Solid Tumors (RECIST v.1.1). The assessment of the toxicity was performed in accordance with the international scale of Common Terminology Criteria for Adverse Events (CTCAE v.5.0). Results: Complete response to cobimetinib was not achieved in any patient. Partial response was established in 62,5% cases. One patient was diagnosed with disease progression in three months after termination of the therapy. The incidence of adverse events was high (75%). The most common side effects were diarrhea (75%), rush (50%) and electrolyte disturbances (37,5%). Summary/Conclusion: Cobimetinib monotherapy is effective in BRAF V600e- negative refractory pediatric LCH patients. The response to the treatment can be delayed. All cases of the toxicity were dose dependant and successfully resolved after dose correction. Further research is needed to define duration of treatment and optimal dosage regimens.
P725: METABOLIC PROPERTIES OF MESENCHYMAL STROMAL CELLS IN MYELODYSPLASTIC SYNDROMES
Authors: E. Balaian, K. Sockel, M. Cross, A. Funk, M. Bornhäuser, T. Chavakis, M. Wobus
Journal: HemaSphere (2022)

Background: The crosstalk between the mutant hematopoietic stem and progenitor cells and the bone marrow microenvironment plays an important role in the pathogenesis of myelodysplastic syndromes (MDS). Mesenchymal stromal cells (MSC) represent one of the key cellular elements in this context. The functional properties of MDS-derived MSCs including impaired hematopoietic support, as well as increased senescence and defective osteogenic differentiation have been extensively studied. Additionally, the detrimental effect of high erythropoietin (Epo) concentration on MDS-MSCs has been demonstrated by our group. However, whether these deficiencies are associated with cellular metabolic changes has not been hitherto addressed. Aims: We aimed to assess the basal metabolic characteristics in MDS-derived MSCs and the effect of Epo on their energetic profile in vitro. Methods: MSC from bone marrow aspirates of patients with MDS (low risk n=3, MDS del5q n=1, chronic myelomonocytic leukemia n=2, high risk n=3) or age-adjusted healthy donors (n=3) were isolated by Ficoll density centrifugation and plastic adherent culture. Metabolic measurements were performed before and after incubation with Epo (50 IU/ml) for 2 days. Seahorse X96 Flux Analyzer (Seahorse Biosciences, Billerica, MA, USA) was used to analyse glucose metabolism by oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Metabolite concentrations were measured in the culture supernatants using NMR spectroscopy. Results: MSC from healthy donors demonstrated a higher OCR/ECAR ratio compared to MDS counterparts (6.19±4,71 vs 1.14±0.28, p=0.005), suggesting enhanced glycolysis engagement of MDS-MSCs. This was confirmed by increased levels of lactate in the culture medium from MDS-MSCs after 48 hours of cultivation (healthy: 3.78±0.28 mM vs MDS: 6.75±2.35 mM, p=0.049), whereas the concentrations of pyruvate, alanine and acetate did not differ. Treatment with Epo resulted in a significant increase of the OCR/ECAR ratio (from 1.14±0.28 to 3.25±1.75, p=0.003) in MDS-MSCs, whereas changes in healthy MSCs were not significant (from 6.19±4,71 to 3.81±1.86, p=0.46). Summary/Conclusion: In contrast to healthy MSCs which rely mainly on mitochondrial respiration, MDS-MSCs preferentially utilize the glycolytic pathway under normoxic conditions in vitro. Epo treatment leads to increased mitochondrial respiration in MDS-MSCs, but not in healthy counterparts. Whether this effect has a causative link to the disturbed function of MDS-MSCs remains to be clarified.
Detection of Marburg Virus Disease in Guinea
Authors: Fara R Koundouno, Liana E Kafetzopoulou, Martin Faye, Annick Renevey, Barrè Soropogui, Kékoura Ifono, Emily V Nelson, Aly A Kamano, Charles Tolno, Giuditta Annibaldis, Saa L Millimono, Jacob Camara, Karifa Kourouma, Ahmadou Doré, Tamba E Millimouno, Fernand M B Tolno, Julia Hinzmann, Hugo Soubrier, Mette Hinrichs, Anke Thielebein, Glaucia Herzer, Meike Pahlmann, Georges A Ki-Zerbo, Pierre Formenty, Anaïs Legand, Michael R Wiley, Ousmane Faye, Moussa M Diagne, Amadou A Sall, Philippe Lemey, Aïssatou Bah, Stephan Günther, Sakoba Keita, Sophie Duraffour, N'Faly Magassouba
Journal: New England Journal of Medicine (2022)

single mutants (i.e., BA.2_L452Q and BA.2_ S704L) had neutralizing-antibody escape that was similar to that of the BA.4/5 and BA.2.12.1 subvariants, with neutralizing-antibody titers that were 14.1% and 26.6% lower, respectively, than those against BA.2 (P>0.05 for both comparisons) (Fig. 1D).Notably, 2 of 30 BA.1-infected but unvaccinated patients (Patients U12 and U13) had high neutralizing-antibody titers against all the variants except BA.4/5, whereas patients who had received a booster dose had broader neutralization against all the variants examined (Fig. S3C andS3D).Overall, these results showed that infection during the BA.1 wave did not appear to offer effective protection against the newly emerged sublineages.In this study, we characterized infectioninduced immunity and vaccine-induced immunity against newly emerged omicron subvariants.Booster vaccination provided sufficient neutralizing-antibody titers against the BA.4/5 and BA.2.12.1 subvariants, albeit to a lower extent than against BA.1 and BA.2. 4,5These findings underscore the importance of booster vaccination for protection against emerging variants.
Patient-Centered Default Opioid Orders—A Path Forward for Postoperative Opioid Stewardship
Authors: M. Kit Delgado
Journal: JAMA Network Open (2022)

interventions. 7 Chua et al 4 measured a wide variety of patient-reported outcomes, including satisfaction with pain control, time to pain resolution, pain scores over time, and anxiety, and there were no statistically significant differences in these outcomes.However, there was a modest but statistically significant increase in sleep disturbance among patients exposed to the lower EHR +
Errors in the Results Section, Table 2, and the Supplement
Journal: JAMA Network Open (2022)

titled "Evaluation of Economic and Health Outcomes Associated With Food Taxes and Subsidies: A Systematic Review and Meta-analysis," 1 published June 1, 2022, there were errors in the Results section, Table 2, and the Supplement.In the Results section, several sentences referring to "diet-related NCDs [noncommunicable diseases]" should have referred to "undernutrition."In Table 2 under the fruit and vegetable subsidy category, the row for diet-related NCDs was deleted, and the direction and statistical significance of estimated outcomes description for that row was added to the undernutrition row.In the Supplement, "noncommunicable disease (NCD)" in eTable 2 was changed to "undernutrition."The article and Supplement have been corrected. 1
P1676: COVID VACCINE INDUCED IMMUNO THROMBOCYTOPENIA AND THROMBOSIS - OBSERVATIONAL STUDY
Authors: S. Gopaluni, C. Ranjith Kumar, S. Koganti, A. Aribandi
Journal: HemaSphere (2022)

Background: Vaccination has been an important strategic tool in helping to bring the COVID pandemic to an end. A multitude of vaccines are available, a few of which have undergone phase 3 trials and been approved for use across the world. In India, Covishield, a viral vector-based RNA vaccine (ChAdOX1) was the most used vaccine. Viral vector vaccines were reported to cause serious thrombotic complications (Vaccine induced thrombocytopenia and thrombosis), especially cerebral sinus venous thrombosis in young females, by generating antibodies against PF4 antigen. Here we report three cases of non-fatal but serious thrombotic complications in patients that received Covishield vaccine. Aims: In this observational study we aimed to study the thrombotic adverse effects following COVID vaccination. Methods: Patients admitted to our 250 bedded multi-specialty hospital with any thrombotic complications were assessed for temporal relationship with Covid vaccination. Results: - Sno Case 1 Case 2 Case 3 Age 47yrs 37yrs 75yrs Sex Male Male Male Underlying condition Membranous nephropathy –Partial remission (urine protein creatinine ratio: 2.4g/g, albumin: 3.4 g/dL) - Diabetes Hypertension Vaccine type Covishield Covishield Covishield Time between Vaccination and effect 2days 6weeks 2days Presentation Syncopal episode Acute upper and peri-umbilical abdominal pain. Right sided abdominal pain. haemodynamically unstable with right ventricular strain pattern. CT abdomen - acute portal vein and superior mesenteric vein thrombosis CT abdomen-acute thrombosis of right main renal artery with infarction of right kidney. CTPA- saddle thrombus Platelet count 100 x 103/cmm 135 x 103/cmm 130 x 103/cmm HIT screen[PF4] - ++ - Treatment Thrombolysis à Rivoroxaban Warfarin Thrombectomy Outcome Alive Alive Alive Summary/Conclusion: Here were described three different cases of thrombosis that presented within 6 week of receiving first dose of Covishield vaccine. A common feature with all of the patients was relatively mild thrombocytopenia, and possibly an underlying predisposition for thrombosis. In one patient we could conclusively prove the presence of HIT antibodies as much was known about VITT by then. The aim of this article is to bring awareness to the wider community about the possible association of vaccination in the context of acute thrombosis. It is imperative that heparin be avoided in these patients. Fondaparinux is a suitable alternative. Further anti-coagulation could be with either warfarin or novel oral anti-coagulants. IVIG was also used in the treatment of some patients with cerebral venous sinus thrombosis.
Rural-Urban Differences in Diabetes Care and Control in 42 Low- and Middle-Income Countries: A Cross-sectional Study of Nationally Representative Individual-Level Data
Authors: David Flood, Pascal Geldsetzer, Kokou Agoudavi, Krishna K. Aryal, Luisa Campos Caldeira Brant, Garry Brian, Maria Dorobantu, Farshad Farzadfar, Oana Gheorghe-Fronea, Mongal Singh Gurung, David Guwatudde, Corine Houehanou, Jutta M. Adelin Jorgensen, Dimple Kondal, Demetre Labadarios, Maja E. Marcus, Mary Mayige, Mana Moghimi, Bolormaa Norov, Gastón Perman, Sarah Quesnel-Crooks, Mohammad-Mahdi Rashidi, Sahar Saeedi Moghaddam, Jacqueline A. Seiglie, Silver K. Bahendeka, Eric Steinbrook, Michaela Theilmann, Lisa J. Ware, Sebastian Vollmer, Rifat Atun, Justine I. Davies, Mohammed K. Ali, Peter Rohloff, Jennifer Manne-Goehler
Journal: Diabetes Care (2022)

Diabetes prevalence is increasing rapidly in rural areas of low- and middle-income countries (LMICs), but there are limited data on the performance of health systems in delivering equitable and effective care to rural populations. We therefore assessed rural-urban differences in diabetes care and control in LMICs.We pooled individual-level data from nationally representative health surveys in 42 countries. We used Poisson regression models to estimate age-adjusted differences in the proportion of individuals with diabetes in rural versus urban areas achieving performance measures for the diagnosis, treatment, and control of diabetes and associated cardiovascular risk factors. We examined differences across the pooled sample, by sex, and by country.The pooled sample from 42 countries included 840,110 individuals (35,404 with diabetes). Compared with urban populations with diabetes, rural populations had ∼15-30% lower relative risk of achieving performance measures for diabetes diagnosis and treatment. Rural populations with diagnosed diabetes had a 14% (95% CI 5-22%) lower relative risk of glycemic control, 6% (95% CI -5 to 16%) lower relative risk of blood pressure control, and 23% (95% CI 2-39%) lower relative risk of cholesterol control. Rural women with diabetes had lower achievement of performance measures relating to control than urban women, whereas among men, differences were small.Rural populations with diabetes experience substantial inequities in the achievement of diabetes performance measures in LMICs. Programs and policies aiming to strengthen global diabetes care must consider the unique challenges experienced by rural populations.
Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients
Authors: Raquel Carbonell, Silvia Urgelés, Melina Salgado, Alejandro Rodríguez, Luis Felipe Reyes, Yuli V. Fuentes, Cristian C. Serrano, Eder L. Caceres, María Bodí, Ignacio Martín-Loeches, Jordi Solé-Violán, Emili Díaz, Josep Gómez, Sandra Trefler, Montserrat Vallverdú, Josefa Murcia, Antonio Albaya, Ana Loza, Lorenzo Socias, Juan Carlos Ballesteros, Elisabeth Papiol, Lucía Viña, Susana Sancho, Mercedes Nieto, M del, Carmen Lorente, Oihane Badallo, Virginia Fraile, Fernando Arméstar, Angel Estella, Paula Abanses, Isabel Sancho, Neus Guasch, Gerard Moreno
Journal: Journal of Infection (2022)
Cancer‐specific survival after diagnosis in men versus women: A pan‐cancer analysis
Authors: Yan He, Yonglin Su, Junsong Zeng, Weelic Chong, Xiaolin Hu, Yu Zhang, Xingchen Peng
Journal: MedComm (2022)

Comprehensive understanding of cancer-specific survival differences in gender is critical for cancer prevention and treatment. Based on the Surveillance Epidemiology and End Results database, we included data from the most prevalent cancers (lung, esophageal, liver, pancreatic, stomach, colorectal, kidney, and bladder cancer). Cox proportional hazards regression models were constructed to estimate hazard ratios, simultaneously adjusting for demographic, clinical, and treatment factors. Overall, male patients had a worse cancer-specific survival than female patients. After adjustment for cancer prevalence with 1:1 matching, gender remained a significant factor in cancer-specific survival. Among the included cancer types, female patients showed survival benefit in lung, liver, colorectal, pancreatic, stomach, and esophageal cancer, and male patients showed better survival in bladder cancer. Except for kidney cancer, the gender disparity was consistent between cancer patients with nonmetastatic and metastatic disease. Overall, gender appears to be a significant factor influencing cancer-specific survival, and the prognosis of female patients is better than male patients in most cancers. This work might inspire the development of strategies for gender-specific precision cancer prevention and treatment.
Impact of biologic therapy on cancer outcomes in patients with immune checkpoint inhibitor–induced bullous pemphigoid
Authors: Jordan T. Said, Jordan Talia, Erin Wei, Arash Mostaghimi, Yevgeniy Semenov, Anita Giobbie-Hurder, Steven T. Chen, Nicole R. LeBoeuf
Journal: Journal of the American Academy of Dermatology (2022)
A 3D Osteosarcoma Model with Bone‐Mimicking Cues Reveals a Critical Role of Bone Mineral and Informs Drug Discovery
Authors: Eva C. González Díaz, Alex G. Lee, Leanne C. Sayles, Criselle Feria, E. Alejandro Sweet‐Cordero, Fan Yang
Journal: Advanced Healthcare Materials (2022)

Abstract Osteosarcoma (OS) is an aggressive bone cancer for which survival has not improved over three decades. While biomaterials have been widely used to engineer 3D soft‐tissue tumor models, the potential of engineering 3D biomaterials‐based OS models for comprehensive interrogation of OS pathology and drug discovery remains untapped. Bone is characterized by high mineral content, yet the role of bone mineral in OS progression and drug response remains unknown. Here, a microribbon‐based OS model with bone‐mimicking compositions is developed to elucidate the role of 3D culture and hydroxyapatite in OS signaling and drug response. The results reveal that hydroxyapatite in 3D is critical to support retention of OS signaling and drug resistance similar to patient tissues and mouse orthotopic tumors. The physiological relevance of this 3D model is validated using four established OS cell lines, seven patient‐derived xenograft (PDX) cell lines and two animal models. Integrating 3D OS PDX models with RNA‐sequencing identified 3D‐specific druggable target, which predicts drug response in mouse orthotopic model. These results establish microribbon‐based 3D OS models as a novel experimental tool to enable discovery of novel therapeutics that would be otherwise missed with 2D model and may serve as platforms to study patient‐specific OS heterogeneity and drug resistance mechanisms.
Clinic and Computed Tomographic Imaging of Lung Pathology in COVID-19 Comorbidity, Tuberculosis and Opportunistic Diseases in Patients with HIV Infection
Authors: A. V. Mishina, V. Yu. Mishin, D. A. Lezhnev, A. L. Sobkin
Journal: Radiology - Practice (2022)

The clinic and computer tomographic imaging of lung pathology in COVID-19 comorbidity, tuberculosis and opportunistic diseases in patients with stage IV of HIV infection, in the phase of progression, in the absence of ART in 29 patients compared with similar 29 patients, but without COVID-19 were studied. It was found that the comorbidity of COVID-19 and tuberculosis, stage IV of HIV infection, in the phase of progression, in the absence of ART is characterized by the generalization of tuberculosis and the development of opportunistic lung diseases, severe clinical picture and visualization with computed tomography of dissemination syndrome, pulmonary pattern pathology and adenopathy, which practically does not differ from patients without COVID-19. It is not possible to diagnose this comorbidity by clinical and radiation methods of research. Special microbiological and molecular genetic methods are needed to study diagnostic material from the respiratory system and other organs in order to prescribe timely etiological treatment.
Podocyte-specific Nlrp3 inflammasome activation promotes diabetic kidney disease
Authors: Khurrum Shahzad, Sameen Fatima, Hamzah Khawaja, Ahmed Elwakiel, Ihsan Gadi, Saira Ambreen, Silke Zimmermann, Peter R. Mertens, Ronald Biemann, Berend Isermann
Journal: Kidney International (2022)

Efficient therapies for diabetic kidney disease (DKD), now the leading cause of kidney failure, are lacking. One hallmark of DKD is sterile inflammation (inflammation in absence of microorganisms), but the underlying molecular mechanisms remain poorly understood. The NLRP3 inflammasome (innate immune system receptors and sensors regulating activation of caspase-1) is a mechanism of sterile inflammation known to be activated by metabolic stimuli and reactive metabolites associated with DKD, including inflammasome activation in podocytes. However, whether NLRP3 inflammasome activation in podocytes contributes to sterile inflammation and glomerular damage in DKD remains unknown. Here, we found that kidney damage, as reflected by increased albuminuria, glomerular mesangial expansion and glomerular basement membrane thickness was aggravated in hyperglycemic mice with podocyte-specific expression of an Nlrp3 gain-of-function mutant (Nlrp3A350V). In contrast, hyperglycemic mice with podocyte-specific Nlrp3 or Caspase-1 deficiency showed protection against DKD. Intriguingly, podocyte-specific Nlrp3 deficiency was fully protective, while podocyte-specific caspase-1 deficiency was only partially protective. Podocyte-specific Nlrp3, but not caspase-1 deficiency, maintained glomerular autophagy in hyperglycemic mice, suggesting that podocyte Nlrp3 exerts both canonical and non-canonical effects. Thus, podocyte NLRP3 inflammasome activation is both sufficient and required for DKD and supports the concept that podocytes exert some immune cell-like functions. Hence, as podocyte NLRP3 exerts non-canonical and canonical effects, targeting NLRP3 may be a promising therapeutic approach in DKD.
Development of anti-somatostatin receptors CAR T cells for treatment of neuroendocrine tumors
Authors: Barbara Mandriani, Eleonora Pellè, Francesco Mannavola, Antonio Palazzo, Renè Massimiliano Marsano, Giuseppe Ingravallo, Gerardo Cazzato, Maria Cecilia Ramello, Camillo Porta, Jonathan Strosberg, Daniel Abate-Daga, Mauro Cives
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Neuroendocrine tumors (NETs) overexpress somatostatin receptors (SSTRs). Methods We developed a second-generation, ligand-based, anti-SSTR chimeric antigen receptor (CAR) incorporating the somatostatin analog octreotide in its extracellular moiety. Results Anti-SSTR CAR T cells exerted antitumor activity against SSTR+NET cell linesin vitro. The killing activity was highly specific, as demonstrated by the lack of CAR T cell reactivity against NET cells engineered to express mutated variants of SSTR2/5 by CRISPR/Cas9. When adoptively transferred in NSG mice, anti-SSTR CAR T cells induced significant antitumor activity against human NET xenografts. Although anti-SSTR CAR T cells could recognize the murine SSTRs as shown by their killing ability against murine NET cells, no obvious deleterious effects on SSTR-expressing organs such as the brain or the pancreas were observed in mice. Conclusions Taken together, our results establish anti-SSTR CAR T cells as a potential candidate for early phase clinical investigations in patients with NETs. More broadly, the demonstration that a known peptide drug can direct CAR T cell targeting may streamline the potential utility of multiple peptide motifs and provide a blueprint for therapeutic applications in a variety of cancers.